Maternal morbidity and mortality: an iceberg phenomenon.

OBJECTIVE: To apply the iceberg model, quantifying absolute and relative incidence, to the four main causes of maternal morbidity and mortality in Ireland: haemorrhage, hypertension, sepsis and thrombosis. DESIGN: Secondary analysis of national data on maternal morbidity and mortality. SETTING: Republic of Ireland. POPULATION OR SAMPLE: Approximately 715 000 maternities, 1 200 000 maternal hospitalisations, 2138 cases of severe maternal morbidity (SMM) and 54 maternal deaths. METHODS: Incidence rates and case-fatality ratios were calculated. MAIN OUTCOME MEASURES: Maternal death, SMM and hospitalisation. RESULTS: At the 'tip of the iceberg', the incidence of maternal death per 10 000 maternities was 0.09 (95% CI 0.03-0.20) due to thrombosis and 0.03 (95% CI 0-0.11) due to haemorrhage, hypertension disorders or sepsis. For one death due to thrombosis there were 35 cases of pulmonary embolism and 257 thrombosis hospitalisations. For one death due to eclampsia, there were 58 eclampsia cases, 13 040 hospitalisations with pre-existing hypertension and 40 781 hospitalisations with gestational hypertension. For one death due to pregnancy-related sepsis, there were 92 cases of septicaemic shock and 9005 hospitalisations with obstetric sepsis. For one maternal death due to haemorrhage, there were 1029 cases of major obstetric haemorrhage and 53 715 maternal hospitalisations with haemorrhage. For every 100 maternities, there were approximately 16 hospitalisations associated with haemorrhage, 12 associated with hypertension disorders, three with sepsis and 0.2 with thrombosis. CONCLUSIONS: Haemorrhage and hypertension disorders are leading causes of maternal morbidity in Ireland but they have very low case fatality. This indicates that these morbidities are managed effectively but their prevention requires more focus. TWEETABLE ABSTRACT: Study shows that haemorrhage and hypertension are main causes of #maternalmorbidity in Ireland. Timely interventions for #maternalhealth and focus on prevention of severe and non-severe morbidities are needed. @NPEC #maternityservices #clinicalaudit #qualityimprovement.

Intrapartum fetal deaths and unexpected neonatal deaths in the Republic of Ireland: 2011 - 2014; a descriptive study.

BACKGROUND: Intrapartum fetal death, the death of a fetus during labour, is a tragic outcome of pregnancy. The intrapartum death rate of a country is reflective of the care received by mothers and babies in labour and it is through analysing these cases that good aspects of care, as well as areas for improvement can be identified. Investigating unexpected neonatal deaths that may be associated with an intrapartum event is also helpful to fully appraise intrapartum care. This is a descriptive study of intrapartum fetal deaths and unexpected neonatal deaths in Ireland from 2011 to 2014. METHODS: Anonymised data pertaining to all intrapartum fetal deaths and unexpected neonatal deaths for the study time period was obtained from the national perinatal epidemiology centre. All statistical analyses were conducted using Statistical package for the Social Sciences (SPSS). RESULTS: There were 81 intrapartum fetal deaths from 2011 to 2014, and 36 unexpected neonatal deaths from 2012 to 2014. The overall intrapartum death rate was 0.29 per 1000 births and the corrected intrapartum fetal death rate was 0.16 per 1000 births. The overall unexpected neonatal death rate was 0.17 per 1000 live births. Major Congenital Malformation accounted for 36/81 intrapartum deaths, chorioamnionitis for 18/81, and placental abruption accounted for eight babies' deaths. Intrapartum asphyxia accounted for eight of the intrapartum deaths. With respect to the neonatal deaths over half (21/36, 58.3%) of the babies died as a result of hypoxic ischaemic encephalopathy. Information is also reported on both maternal and individual baby demographics. CONCLUSIONS: This is the first detailed descriptive analysis of intrapartum deaths and unexpected intrapartum event related neonatal deaths in Ireland. The corrected intrapartum fetal death rate was 0.16 per 1000 births. Despite our results being based on the best available national data on intrapartum deaths and unexpected neonatal deaths, we were unable to identify if any of these deaths could have been prevented. A more formal confidential inquiry based system is necessary to fully appraise these cases.

Healthcare professionals' response to intrapartum death: a cross-sectional study.

BACKGROUND: Exposure to adverse perinatal events can impact on the way healthcare professionals (HCPs) provide patient care. The aim of this study was to document the experiences of HCPs following exposure to intrapartum death (IPD), to identify opinions surrounding education and suitable support strategies, and to ascertain if involvement with an IPD had any impact on clinical practice. METHODS: A questionnaire study, with open and closed questions, was developed and set in a tertiary maternity hospital. Consultant obstetricians, trainee obstetricians and midwives were invited to participate. Respondents were questioned about the impact that an intrapartum death had on them, the support they received in the immediate aftermath and their opinions regarding ongoing education and training in the areas of intrapartum death and self-care. RESULTS: Eighty percent of HCPs in our study had a direct involvement with an IPD. Most (82%) HCPs received no training in dealing with IPD while 94% had no education on self-care strategies. Despite it being desired by most (80%), debriefing was offered to just 11% of HCPs who were involved in an IPD. Three main qualitative themes emerged from the data; the personal impact of IPDs on HCPs, implications for professional practice and future patient care, and the importance on non-judgemental support. CONCLUSION: Maternity hospitals need to improve their support structures for HCPs following an IPD. It is hoped that this study will inform future educational practice and identify potential support strategies.

Surgical Site Infection after Caesarean Section? There Is an App for That: Results from a Feasibility Study On Costs and Benefits.

Surgical site infections (SSIs) are one of the most common and, yet, preventable healthcare associated infections. In Ireland, the rate of Caesarean section (CS) is increasing, while postpartum hospital stay is decreasing, adversely affecting SSI among women. There is much need to develop post-discharge surveillance which can effectively monitor, detect, and arrange treatment for affected women. The use of modern technology to survey SSI following discharge from hospital remains unexplored. We report the results of a feasibility study which investigates whether an integrated mobile application (hereafter, app) is more cost-beneficial than a stand-alone app or telephone helpline at surveying SSI following CS. We find women prefer the integrated app (47.5%; n=116/244) over the stand-alone app (8.2%; n=20/244) and telephone helpline (18.0%; 44/244), although there is no significant difference in women's valuation of these services using willingness to pay techniques. The stand-alone app is the only cost-beneficial service due to low labour costs. Future research should employ alternative measures when evaluating the benefits of the health technology. The use of a mobile app as a mechanism for postpartum care could represent a considerable advancement towards technological health care.

Women's experience of maternal morbidity: a qualitative analysis.

BACKGROUND: Maternal morbidity refers to pregnancy-related complications, ranging in severity from acute to chronic. In Ireland one in 210 maternities will experience a severe morbidity. Yet, how women internalize their experience of morbidity has gone largely unexplored. This study aimed to explore women's experiences of maternal morbidity. METHODS: A qualitative semi-structured interview format was utilized. Purposive sampling was used to recruit 14 women with a maternal morbidity before, during or after birth; nine women were diagnosed with one morbidity including hypertensive disorders, haemorrhage, placenta praevia and gestational diabetes whereas five women were diagnosed with two or more morbidities. Thematic analysis was employed as the analytic strategy. RESULTS: Four superordinate themes were identified: powerlessness, morbidity management, morbidity treatment and socio-behavioural responses to morbidities. Women were accepting of the uncontrollable nature of the adverse outcome experienced. While being treated for trauma, women were satisfied to relinquish their autonomy to ensure the safety of themselves and their babies. However, these events were debilitating. Women's inability to control their own bodies, as a result of the morbidity, contributed to high levels of frustration and anxiety. Morbidities impacted greatly on women's quality of life and sometimes these effects persisted for a prolonged period after delivery. Women felt that they were provided very little information on the practicalities of living with their condition; many were uncertain how to manage their morbidities in the home setting. CONCLUSION: Healthcare providers should ensure that women who experience a maternal morbidity are fully debriefed and have sufficient information on the morbidity including ongoing care and expectations prior to discharge.

Time to subsequent live birth according to mode of delivery in the first birth.

OBJECTIVE: To estimate the rate and time to next live birth by mode of delivery. DESIGN: Hospital-based cohort. SETTING: Aarhus University Hospital (AUH), Denmark. POPULATION: All pregnant women attending AUH were invited to enroll in the Aarhus Birth Cohort (ABC) study between 1989 and 2010 (n = 91,625). METHODS: Women were followed from their first live birth until the subsequent live birth or until censoring due to study end using Cox regression models. MAIN OUTCOME MEASURES: Rate and time to subsequent live birth according to mode of delivery. RESULTS: 46,162 index live births were identified, of which 22,462 (49%) had a subsequent live birth. Women with any type of caesarean had a 6% reduction in the rate of subsequent live birth (HR 0.94, 95% CI 0.89, 0.98), which remained unchanged in the analysis by type (emergency, HR 0.95, 95% CI 0.89, 1.02; elective, HR 0.91, 95% CI 0.85, 0.98) compared with women who had a spontaneous vaginal delivery (SVD). Operative vaginal delivery was associated with an 8% reduction in subsequent live birth rates (HR 0.92, 95% CI 0.86, 0.98) and vaginal delivery complicated by shoulder dystocia with a 19% reduction compared with SVD. Median time to next birth in days was shortest in women with a first caesarean (994 days, 95% CI 973, 1026) and longest in women with a vaginal delivery complicated by shoulder dystocia (1065 days, 95% CI 994, 1191). In women with planned pregnancies, the shortest median time to second birth was in women with breech vaginal deliveries (859 days, 95% CI 737, 1089) and the longest in women with vaginal deliveries complicated by shoulder dystocia (1193 days, 95% CI 1028, 1430). CONCLUSION: The impact of mode of delivery on subsequent rate and time to next birth was minimal in this study. The greatest reduction was among women with assisted vaginal delivery complicated by shoulder dystocia. This study is strengthened by data on pregnancy planning as well as information on complications of pregnancy, delivery and neonatal morbidities, all of which may influence a woman's decision on subsequent birth.

Caesarean section and subsequent ectopic pregnancy: a systematic review and meta-analysis.

BACKGROUND: Caesarean section rates are increasing worldwide, and the long-term effects are unknown. OBJECTIVE: To evaluate the risk of subsequent ectopic pregnancy in women with a previous caesarean section, compared with vaginal delivery. SEARCH STRATEGY: Systematic review of the literature using CINAHL, the Cochrane Library, Embase, Medline, PubMed, SCOPUS and Web of Knowledge, published from 1945 until 17 July 2011. SELECTION CRITERIA: Cohort and case-control designs reporting on the mode of delivery and subsequent ectopic pregnancy. Two reviewers independently assessed the titles, abstracts, and full articles to identify eligible studies, using a standardised data collection form, and also assessed the study quality. Reference lists of the studies included were also cross-checked. DATA COLLECTION AND ANALYSIS: Odds ratios (ORs) were combined using a random-effect model to estimate the overall association between caesarean section delivery and the risk of subsequent ectopic pregnancy. MAIN RESULTS: Thirteen studies were included, which recruited a total of 61,978 women. Five studies reported adjustment for confounding factors, and the pooled OR of subsequent ectopic pregnancy following a caesarean section was 1.05 (95% CI 0.51-2.15). The removal of one study that reported outlier results yielded a pooled OR of 0.82 (95% CI 0.42-1.61). The pooled crude OR for all 13 studies was 1.36 (95% CI 0.99-1.88). AUTHOR'S CONCLUSIONS: This review found no evidence of an association between prior caesarean section delivery and the occurrence of a subsequent ectopic pregnancy, but the studies included were of poor or variable quality, and only a small number adjusted for potential confounding factors. Further research of a higher methodological quality is required to assess any potential association between mode of delivery and subsequent ectopic pregnancy.

Increasing trends in atonic postpartum haemorrhage in Ireland: an 11-year population-based cohort study.

OBJECTIVE: To derive nationally representative incidence rates of postpartum haemorrhage (PPH), and to investigate trends associated with method of delivery, blood transfusion and morbidly adherent placenta (accreta, percreta and increta). DESIGN: Population-based retrospective cohort study. SETTING: Republic of Ireland. POPULATION: Childbirth hospitalisations during the period 1999-2009. METHODS: International Classification of Diseases (ICD)-9-CM and ICD-10-AM diagnostic codes from hospital discharge records were used to identify cases of PPH. Significant temporal trends in PPH incidence were determined using Cochrane-Armitage tests for trend. Log-binomial regression was conducted to assess annual changes in the risk of PPH diagnosis, with adjustment for potential confounding factors. MAIN OUTCOME MEASURES: PPH, uterine atony, blood transfusion and morbidly adherent placenta. RESULTS: A total of 649,019 childbirth hospitalisations were recorded; 2.6% (n = 16,909) included a diagnosis of PPH. The overall PPH rate increased from 1.5% in 1999 to 4.1% in 2009; atonic PPH rose from 1.0% in 1999 to 3.4% in 2009. Significant increasing trends in atonic PPH rates were observed across vaginal, instrumental, and emergency and elective caesarean deliveries (P < 0.001). The rate of atonic PPH co-diagnosed with blood transfusion also significantly increased (P < 0.001). Relative to 1999, the risk of atonic PPH in 2009 was three-fold increased (adjusted RR 3.03; 95% CI 2.76-3.34). Women diagnosed with a morbidly adherent placenta had a markedly higher risk of total PPH (unadjusted RR 13.14; 95% CI 11.43-15.11). CONCLUSIONS: Increasing rates of atonic PPH highlight the pressing need for research and for clinical audit focusing on aetiological factors, preventative measures and quality of care, to guide current clinical practice.

The management of reduced fetal movements in an uncomplicated pregnancy at term: results from an anonymous national online survey in the Republic of Ireland.

There is currently inconsistent evidence and clinical guidance on how to best manage a pregnancy complicated by reduced fetal movements. This novel, web-based, anonymous questionnaire evaluated 96 assessment and management approaches from doctors working in obstetrics in the Republic of Ireland who were presented with a clinical scenario of a primigravida concerned about reduced fetal movements at 39+3 weeks' gestation. This study identified a lack of clinical practice guidelines available in maternity hospitals in the Republic of Ireland. We demonstrated that almost all clinicians applied more than one assessment method and that most incorporated a cardiotocograph into their assessment. There was a low uptake of simple symphysio-fundal height measurement and high usage of kickcharts. The minority of clinicians admitted or induced their patients. This survey identified the need for national and international guidelines to ensure safe antepartum care and delivery.

Timing of birth related to obstetric practice and neonatal outcome.

Several studies have reported time of birth is associated with differences in obstetric practice. We investigated the relationship between timing of birth and obstetric and neonatal outcomes, to help plan working patterns under European Working Time Directive (EWTD) legislation. This was a retrospective observational study undertaken in a tertiary-level university teaching hospital. Data were derived from the labour ward register of births for all women who delivered after 24weeks gestation in 2004. Births during on-call hours refer to those that occurred at weekends and after 1630 and before 0830 on weekdays. The majority of infants, 67.3%, were born in on-call hours. Infants were more likely to be delivered by ventouse(p<0.0001), but there was no difference in caesarean section(CS) rates. 83.0% of operative deliveries performed for failure to advance in the second stage of labour took place in on-call hours, as did 77.5% of emergency CS for fetal distress. 38.9% of infants born during on-call hours on weekdays followed induced labours, compared to 24.7% of births at weekends and 17.7% of births in non on-call hours(p<0.001), while 80.0% of deliveries by emergency CS after induction occurred during on-call hours. The majority of perinatal deaths occurred among infants born during on-call hours, even when excluding congenital malformations, and most infants with low Apgar scores were born during on-call hours. Complicated deliveries were more likely to occur in on-call hours. This study confirms previous reports that time of birth impacts on neonatal outcome. Increased demands on staff working out-of-hours have implications for healthcare, staffing and implementation of new working hours under EWTD legislation.

Development of an expressed sequence tag (EST) resource for wheat (Triticum aestivum L.): EST generation, unigene analysis, probe selection and bioinformatics for a 16,000-locus bin-delineated map.

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid (2n = 6x = 42) wheat genome (Triticum aestivum L.). Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags (ESTs) representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection (113,220 ESTs). Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of ESTs into contigs. These contigs plus singletons (unassembled ESTs) were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5' and 3' sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics.

Chromosome bin map of expressed sequence tags in homoeologous group 1 of hexaploid wheat and homoeology with rice and Arabidopsis.

A total of 944 expressed sequence tags (ESTs) generated 2212 EST loci mapped to homoeologous group 1 chromosomes in hexaploid wheat (Triticum aestivum L.). EST deletion maps and the consensus map of group 1 chromosomes were constructed to show EST distribution. EST loci were unevenly distributed among chromosomes 1A, 1B, and 1D with 660, 826, and 726, respectively. The number of EST loci was greater on the long arms than on the short arms for all three chromosomes. The distribution of ESTs along chromosome arms was nonrandom with EST clusters occurring in the distal regions of short arms and middle regions of long arms. Duplications of group 1 ESTs in other homoeologous groups occurred at a rate of 35.5%. Seventy-five percent of wheat chromosome 1 ESTs had significant matches with rice sequences (E < or = e(-10)), where large regions of conservation occurred between wheat consensus chromosome 1 and rice chromosome 5 and between the proximal portion of the long arm of wheat consensus chromosome 1 and rice chromosome 10. Only 9.5% of group 1 ESTs showed significant matches to Arabidopsis genome sequences. The results presented are useful for gene mapping and evolutionary and comparative genomics of grasses.

Group 3 chromosome bin maps of wheat and their relationship to rice chromosome 1.

The focus of this study was to analyze the content, distribution, and comparative genome relationships of 996 chromosome bin-mapped expressed sequence tags (ESTs) accounting for 2266 restriction fragments (loci) on the homoeologous group 3 chromosomes of hexaploid wheat (Triticum aestivum L.). Of these loci, 634, 884, and 748 were mapped on chromosomes 3A, 3B, and 3D, respectively. The individual chromosome bin maps revealed bins with a high density of mapped ESTs in the distal region and bins of low density in the proximal region of the chromosome arms, with the exception of 3DS and 3DL. These distributions were more localized on the higher-resolution group 3 consensus map with intermediate regions of high-mapped-EST density on both chromosome arms. Gene ontology (GO) classification of mapped ESTs was not significantly different for homoeologous group 3 chromosomes compared to the other groups. A combined analysis of the individual bin maps using 537 of the mapped ESTs revealed rearrangements between the group 3 chromosomes. Approximately 232 (44%) of the consensus mapped ESTs matched sequences on rice chromosome 1 and revealed large- and small-scale differences in gene order. Of the group 3 mapped EST unigenes approximately 21 and 32% matched the Arabidopsis coding regions and proteins, respectively, but no chromosome-level gene order conservation was detected.

A 2600-locus chromosome bin map of wheat homoeologous group 2 reveals interstitial gene-rich islands and colinearity with rice.

The complex hexaploid wheat genome offers many challenges for genomics research. Expressed sequence tags facilitate the analysis of gene-coding regions and provide a rich source of molecular markers for mapping and comparison with model organisms. The objectives of this study were to construct a high-density EST chromosome bin map of wheat homoeologous group 2 chromosomes to determine the distribution of ESTs, construct a consensus map of group 2 ESTs, investigate synteny, examine patterns of duplication, and assess the colinearity with rice of ESTs assigned to the group 2 consensus bin map. A total of 2600 loci generated from 1110 ESTs were mapped to group 2 chromosomes by Southern hybridization onto wheat aneuploid chromosome and deletion stocks. A consensus map was constructed of 552 ESTs mapping to more than one group 2 chromosome. Regions of high gene density in distal bins and low gene density in proximal bins were found. Two interstitial gene-rich islands flanked by relatively gene-poor regions on both the short and long arms and having good synteny with rice were discovered. The map locations of two ESTs indicated the possible presence of a small pericentric inversion on chromosome 2B. Wheat chromosome group 2 was shown to share syntenous blocks with rice chromosomes 4 and 7.

Deletion mapping of homoeologous group 6-specific wheat expressed sequence tags.

To localize wheat (Triticum aestivum L.) ESTs on chromosomes, 882 homoeologous group 6-specific ESTs were identified by physically mapping 7965 singletons from 37 cDNA libraries on 146 chromosome, arm, and sub-arm aneuploid and deletion stocks. The 882 ESTs were physically mapped to 25 regions (bins) flanked by 23 deletion breakpoints. Of the 5154 restriction fragments detected by 882 ESTs, 2043 (loci) were localized to group 6 chromosomes and 806 were mapped on other chromosome groups. The number of loci mapped was greatest on chromosome 6B and least on 6D. The 264 ESTs that detected orthologous loci on all three homoeologs using one restriction enzyme were used to construct a consensus physical map. The physical distribution of ESTs was uneven on chromosomes with a tendency toward higher densities in the distal halves of chromosome arms. About 43% of the wheat group 6 ESTs identified rice homologs upon comparisons of genome sequences. Fifty-eight percent of these ESTs were present on rice chromosome 2 and the remaining were on other rice chromosomes. Even within the group 6 bins, rice chromosomal blocks identified by 1-6 wheat ESTs were homologous to up to 11 rice chromosomes. These rice-block contigs were used to resolve the order of wheat ESTs within each bin.

A chromosome bin map of 2148 expressed sequence tag loci of wheat homoeologous group 7.

The objectives of this study were to develop a high-density chromosome bin map of homoeologous group 7 in hexaploid wheat (Triticum aestivum L.), to identify gene distribution in these chromosomes, and to perform comparative studies of wheat with rice and barley. We mapped 2148 loci from 919 EST clones onto group 7 chromosomes of wheat. In the majority of cases the numbers of loci were significantly lower in the centromeric regions and tended to increase in the distal regions. The level of duplicated loci in this group was 24% with most of these loci being localized toward the distal regions. One hundred nineteen EST probes that hybridized to three fragments and mapped to the three group 7 chromosomes were designated landmark probes and were used to construct a consensus homoeologous group 7 map. An additional 49 probes that mapped to 7AS, 7DS, and the ancestral translocated segment involving 7BS also were designated landmarks. Landmark probe orders and comparative maps of wheat, rice, and barley were produced on the basis of corresponding rice BAC/PAC and genetic markers that mapped on chromosomes 6 and 8 of rice. Identification of landmark ESTs and development of consensus maps may provide a framework of conserved coding regions predating the evolution of wheat genomes.

A chromosome bin map of 16,000 expressed sequence tag loci and distribution of genes among the three genomes of polyploid wheat.

Because of the huge size of the common wheat (Triticum aestivum L., 2n = 6x = 42, AABBDD) genome of 17,300 Mb, sequencing and mapping of the expressed portion is a logical first step for gene discovery. Here we report mapping of 7104 expressed sequence tag (EST) unigenes by Southern hybridization into a chromosome bin map using a set of wheat aneuploids and deletion stocks. Each EST detected a mean of 4.8 restriction fragments and 2.8 loci. More loci were mapped in the B genome (5774) than in the A (5173) or D (5146) genomes. The EST density was significantly higher for the D genome than for the A or B. In general, EST density increased relative to the physical distance from the centromere. The majority of EST-dense regions are in the distal parts of chromosomes. Most of the agronomically important genes are located in EST-dense regions. The chromosome bin map of ESTs is a unique resource for SNP analysis, comparative mapping, structural and functional analysis, and polyploid evolution, as well as providing a framework for constructing a sequence-ready, BAC-contig map of the wheat genome.

Current perspectives on benefits and risks of hormone replacement therapy.

Hormone replacement therapy with estrogen alone or with added progestin relieves menopausal symptoms and physical changes associated with depleted endogenous estrogen levels. Estrogen replacement has also demonstrated a clear benefit in the prevention of osteoporosis. Hormone replacement therapy with added progestin maintains spinal bone density, protects against postmenopausal hip fractures, and provides these benefits even when therapy is started after age 60. More recently, additional benefits have emerged. Current estrogen and hormone replacement therapy users have a 34% reduction in the risk of colorectal cancer and a 20% to 60% reduction in the risk of Alzheimer's disease. Until recently, the body of evidence indicated that hormone replacement therapy with estrogen only reduced cardiovascular disease risk by 40% to 50% in healthy patients; whether the findings of 3 ongoing trials will change this conclusion is pending availability of the final results. The many benefits of estrogen and hormone replacement therapy must be weighed against a slight increase in the risk of breast cancer diagnosis with use for 5 or more years, but which disappears following cessation of therapy. Overall, estrogen and hormone replacement therapy improves the quality of life and increases life expectancy for most menopausal women.

The new genetic era in reproductive medicine: possibilities, probabilities and problems.

The "New Genetic Era" will be a period of enormous exponential growth in our knowledge of the structure and function of the basic information blocks of life. The Human Genome Project will soon provide a complete and accurate sequence of the human genome. This will give us an abundance of basic genetic knowledge and provide a molecular understanding of disease, allowing for improved diagnosis and more sensitive and specific screening for disease. This will, we hope, lead to better treatments, prevention and cures through gene therapy, patient-specific drug design, and earlier and more specific behavioral interventions to prevent disease. With this information comes a complexity of legal, ethical and social concerns about potential use and abuse. The public has expressed its concerns about the potential for genetic discrimination. However, genetic information is enhancing our knowledge as to the causes of infertility, allowing diagnosis of more diseases in the prenatal period, and may aid our identification of patients at increased risk for breast and ovarian cancer. Doctors involved in reproductive medicine must become knowledgeable about the new genetic era so as to offer our patients the most appropriate and informed care.